Process for the manufacture of



i atented May 5, 1953 raoosss roe THEMANUFAQTURE or rraazotonss,

Max Schmid, Riehen, and Eduard Moser, Basel, Switzerland, assignors to Ci'ba Limited, Basel, Switzerland, a swisslfirm No Drawing. Application October 19, 1950, Serial No. IQL'WZG. In Switzerland November 8, 1949 It is known that pyrazolones can be obtained by condensing c-keto-carboxylic acid amides (acyl-acetic acid amides) with hydrazines. However, this process has found hardly any technical application, as the corresponding pyazolones are generally made by condensing the c-lcetomarboxylic acid esters with hydrazine or substitution products thereof.

The present invention is based on the observation that a group of pyrazolones, which have been obtainable hitherto only with diificulty or in poor yields or by complicated methods, namely pyrazolones which still contain in the molecule a free amino group, can be made in an especially simple manner by condensing an aryl-hydrazine, i I

which contains a free amino group, with acetoacetic acid amide.

The aryl-hydrazines containing a free amino group used as starting materials in the'present process may contain, for example, the hydrazine group (--NH--NI{2) and also a free amino group in one and the same benzene nucleus. The aryl residue of the aryl-hydraaine may contain several rings, for example, benzene rings fused or linked together. As examples of suitable starting materials there may be mentioned l-aminm l hyclrazine-stilbene-Z:2'-disulionic acid and 4 amino -dinhenyli'hydrazine and especially meta-amino-phenyl-hydrazine.

The acetoacetic acid amide also require-d for the reaction can be obtained in a simple manner by reacting diketene with ammonia. The above mentioned hydrazine compounds containing an amino group are also obtainable by known methods (see for example Eeilsteins Handbuch dcr Organischen Chemie vo XV, page 651 and US. Patents 2,195,785 and 2,195,786).

The-condensation of the hydrazine compounds containing an amino group with acetoacetic acid amide can be carried out as desired in a medium containing an organic solvent, but in most cases in a simple manner in an aqueous medium, which may, if desired, also contain an organic solvent miscible with water, such as an alcohol of low molecular weight. The reaction takes place surprisingly rapidly in most cases at a low tempera.- ture, for example, at room temperature. In many cases it is of advantage to conduct the condensation in an approximately neutral to weakly acid medium, for example an acetic acidme- 3 Claims. (c1. Mill-310$ dium. Dependin on the starting material used, for example, on whether it is a monoor (11115 drochloride of a hydrazine containing an amino group, it may be of advantage to adjust the pit of the solution to a favorable value by the addition of an alkali or an acid or buffering 00231 pound such as sodium acetate.

The resulting pyrazolones, which still contain a free amino group, are in part known and in part new. They are valuable intermediate products especially for the manufacture of aso-clyestuffs.

It is surprising that the present process proceeds smoothly, especially as corresponding re actions with o-keto-carboxylic esters are much more diflicult to carry out or lead to large quantities of undesired, for example, resinous, lay-products.

The following examples illustrate the invention, the parts and percentages being by weight unless otherwise stated and the relationship of parts by weight to parts by volume being the same as that of the kilogram to the liter.

Example 1 19.6 parts of the dihydrochloriile of metaamino-phenyi-hydiazine are dissolved in ice parts of water at room temperature and 28 parts of" crystalline sodium acetate are added. 166 parts by volume of an aqueous solution of 1c per cent. strength of acetoacetic a id amide (which may be prepared for example, by neutralizing aqueous solution of ammonia with diketene while cooling with ice-water) are poured in while stirring. The condensation to meta-aminmphenyl- S-methyl-E-pyrazolone of the formula takes place rapidly. The whole is further stirred for 2-3 hours and the pyrazolone is precipitated by the addition of sodium chloride. It is a yellow brown powder which, when titrated with diazo-benzene consumes, per mol, one mol of the reagent and when titrated with nitrous acid consumes, per mol, 2 mols of the reagent.

Example 2 45.3 parts of the dihydrochloride of 4-arninoi'-hydrazine-stilbene-2:2'-disulfonic acid are dissolved in 200 parts of Water with 46 parts of a sodium hydroxide solution of 30 per cent. strength at room temperature and 1-00 parts by volume of an aqueous solution of 10 per cent. strength of acetoacetic acid amide are added. 10 parts of glacial acetic acid are poured into the clear solution and the whole is stirred for 2-3 hours until hydrazine can no longer be detected. Then sodium carbonate (about 20 parts) is added until the solution shows alkaline reaction to Brilliant Yellow, and the solution is heated to 50 C.

4. amino stilbene 2:2 disulfonic acid 4' (3-methyl-5-pyrazolone) of the formula SOaH 503B Example 3 27.2 parts of dihydrochloride of 4-aminodiphenyl-4'hydrazine are stirred in 250 parts of alcohol of about 50 per cent. strength at room temperature, and 27 parts by volume of sodium hydroxide solution of 30 per cent. strength are added. 8 parts of glacial acetic acid and then 10.1 parts of acetoacetic acid amide (which is obtained, for example, by evaporating the aqueous solution in vacuo at 50-60 C.) are added to the thinly liquid suspension. The condensation to form the pyrazolone takes place after stirring for a short time. About 160 parts of sodium hydroxide solution of per cent strength are then poured in, and the solution which is weakly alkaline to phenolphthalein is filtered to remove impurities, and 4-amino-diphenyl-4-(3-methyl-5- pyrazolone) of the formula II I o H is precipitated by adding suflicient hydrochloric acid to produce a Weakly acid reaction to Congo. The product is yellow-brown, and when titrated with diazo-benzene consumes, per mol, one mol of the reagent, and when titrated with nitrous acid consumes, per mol, 2 mols of the reagent.

While the invention has been illustrated by means of examples ofamino-aryl-hydrazines of the benzene, diphenyl and stilbene series because the resulting pyrazolones' are especially valuable products, it is to be understood that the present process can be used with other amino-arylhydrazines, for example, of the naphthalene series as well, provided always that both the hy- 4 drazine group and the amino group are directly bound to an aromatic radical.

What we claim is:

1. A process for the manufacture of a pyrazolone containing a free amino group, which comprises condensin in an aqueous medium of about neutral to weakly acid reaction, one molecular proportion of an aryl-hydrazine corresponding to the formula wherein R stands for an aryl radical containing an aromatically bound free amino group with one molecular proportion of acetoacetic acid amide, and recovering the amino-aryl pyrazolone thus formed.

2. A process for the manufacture of a pyrazolone containing a free amino group, which comprises condensing in an aqueous medium containing a substantial proportion of an alcohol .of. low molecular weight for promoting the solubility of the reactants, the said medium being of about neutral to weakly acid reaction, one molecular proportion of an aryl-hydrazine corresponding to the formula wherein R stands for an aryl radical containing an aromatically bound free amino group with one molecular proportion of acetoacetic acid amide, and recovering the amino-aryl pyrazolone thus formed.

3. A process for the manufacture of a pyrazolone containing a free amino group, which comprises condensing one molecular proportion of a phenyl-hydrazine of the formula phenyl--NH-Nm containing a free amino group as a substituent in the phenyl radical with one molecular proportion of acetoacetic acid amide, and recovering the amino-phenyl pyrazolone thus formed.

4. A process for the manufacture of a pyrazclone containing a free amino group, which comprises condensing one molecular proportion of a diphenyl-hydrazine of the formula diphenylNHNHz containing a free amino group as a substituent in the diphenyl radical with one molecular proportion 01" acetoacetic acid amide, and recovering the amino-diphenyl pyrazolone thus formed.

5. A process for the manufacture of a pyrazclone containing a free amino group, which comprises condensing one molecular proportion of a stilbene-hydrazine of the formula stilbene-NH-Nlh containing a free amino group as a substituent in the stilbene radical with one molecular proportion of acetoacetic acid amide, and recovering the amino-stilbene pyrazolone thus formed.

6. A process for the manufacture of metaamino phenyl 3 methyl 5 pyrazolone, which comprises condensing in an aqueous medium of about neutral to weakly acid reaction one molecular proportion of meta-amino-phenylhydrazine with one molecular proportion of acetoacetic acid amide, and recovering the product thus formed.

7. A proces for the manufacture of 4-aminostilbene 2:2 disulfonic acid 4' (3 methyl.- 5-pyrazolone), which comprises condensing in an aqueous medium of about neutral to weakly acid reaction one molecular proportion of 4- amino 4' hydrazino stilbene 2:2 disulfonic acid with one molecular proportion of acetoacetic acid amide, and recovering the product thus formed.

8. A process for the manufacture of 4-aminodiphenyl 4E (3 methyl 5 pyrazolone), which comprises condensing in an aqueous medium or about neutral to Weakly acid reaction one molecular proportion of 4-amino-dipheny1- 4'-hydrazine with one molecular proportion of acetoacetic acid amide, and recovering the prodnot thus formed.

MAX SCI-IMID. EDUARD MOSER.

References Cited in the file Of this patent UNITED STATES PATENTS Name Date Ostromislensky Oct. 15, 1935 Number 6 Number Name Date 2,017,815 Johnston Oct. 15, 1935 2,227,654 Lecher et a1 Jan. '7, 1941 v FOREIGN PATENTS A) Number Country Date 41,936 Germany Jan. 31, 1888 OTHER REFERENCES Bull. Soc. Chirn. (4=)1, p. 1071.

10 Beilstein, Organische Chemie, v01. 15, p. 344. 

1. A PROCESS FOR THE MANUFACTURE OF A PYRAZOLONE CONTAINING A FREE AMINO GROUP, WHICH COMPRISES CONDENSING IN AN AQUEOUS MEDIUM OF ABOUT NEUTRAL TO WEAKLY ACID REACTION, ONE MOLECULAR PROPORTION OF AN ARYL-HYDRAZINE CORRESPONDING TO THE FORMULA 